Spatially resolved rewiring of mitochondria-lipid droplet interactions in hepatic lipid homeostasis DOI Creative Commons
Sun Woo Sophie Kang,

Lauryn A. Brown,

Colin B. Miller

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Abstract Hepatic lipid accumulation, or Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), is a significant risk factor for liver cancer. Despite the rising incidence of MASLD, underlying mechanisms steatosis and lipotoxicity remain poorly understood. Interestingly, accumulation also occurs during fasting, driven by mobilization adipose tissue-derived fatty acids into liver. However, how hepatocytes adapt to increased flux nutrient deprivation what differently in MASLD not known. To investigate differences handling response deficiency excess, we developed novel single-cell tissue imaging (scPhenomics) technique coupled with spatial proteomics. Our investigation revealed extensive remodeling droplet (LD) mitochondrial topology dietary conditions. Notably, fasted mice exhibited mitochondria-LD interactions, which were rarely observed Western Diet (WD)-fed mice. Spatial proteomics showed an increase PLIN5 expression, known mediator LD-mitochondria interaction, fasting. examine functional role interaction on handling, overexpressed variants. We found that phosphorylation state impacts its capacity form contact sites. S155A promoted organelle triglyceride (TG) synthesis, LD expansion fed control diet. Conversely, S155E expressing cells had fewer LDs sites contained less TG. Wild-type (WT) overexpression WD-fed reduced improved redox despite continued WD consumption. These findings highlight importance interactions metabolism, revealing critical mechanism maintain homeostasis metabolic stress. study underscores potential utility targeting therapeutic intervention.

Language: Английский

Molecular mechanisms of lipid droplets-mitochondria coupling in obesity and metabolic syndrome: insights and pharmacological implications DOI Creative Commons
Chunmei Zhang, Mingxuan Zheng,

Runlin Bai

et al.

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 11, 2024

Abnormal lipid accumulation is a fundamental contributor to obesity and metabolic disorders. Lipid droplets (LDs) mitochondria (MT) serve as organelle chaperones in metabolism energy balance. LDs play crucial role storage mobilization, working conjunction with MT regulate within the liver, brown adipose tissue, skeletal muscle, thereby maintaining homeostasis. The novelty of our review comprehensive description LD interaction mechanisms. We also focus on current drugs that target this metabolism, which provide novel approaches for related disorder treatment.

Language: Английский

Citations

0
Spatially resolved rewiring of mitochondria-lipid droplet interactions in hepatic lipid homeostasis DOI Creative Commons
Sun Woo Sophie Kang,

Lauryn A. Brown,

Colin B. Miller

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Abstract Hepatic lipid accumulation, or Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), is a significant risk factor for liver cancer. Despite the rising incidence of MASLD, underlying mechanisms steatosis and lipotoxicity remain poorly understood. Interestingly, accumulation also occurs during fasting, driven by mobilization adipose tissue-derived fatty acids into liver. However, how hepatocytes adapt to increased flux nutrient deprivation what differently in MASLD not known. To investigate differences handling response deficiency excess, we developed novel single-cell tissue imaging (scPhenomics) technique coupled with spatial proteomics. Our investigation revealed extensive remodeling droplet (LD) mitochondrial topology dietary conditions. Notably, fasted mice exhibited mitochondria-LD interactions, which were rarely observed Western Diet (WD)-fed mice. Spatial proteomics showed an increase PLIN5 expression, known mediator LD-mitochondria interaction, fasting. examine functional role interaction on handling, overexpressed variants. We found that phosphorylation state impacts its capacity form contact sites. S155A promoted organelle triglyceride (TG) synthesis, LD expansion fed control diet. Conversely, S155E expressing cells had fewer LDs sites contained less TG. Wild-type (WT) overexpression WD-fed reduced improved redox despite continued WD consumption. These findings highlight importance interactions metabolism, revealing critical mechanism maintain homeostasis metabolic stress. study underscores potential utility targeting therapeutic intervention.

Language: Английский

Citations

0